The thalamus is both a major relay station of sensory and perceptual information to the cortex as well as an important reciprocal participant in cortical action. These roles, both relevant to the sensory processing and executive action deficits in schizophrenia, make the thalamus a leading candidate structure for the defective link in the neural circuits involved in the disease diathesis. During the first 3 years of this project we have developed reliable methods for outlining the medial dorsal nucleus, the pulvinar, and the centromedian nucleus and applied these techniques to the high-resolution MRI of 101 subjects, 41 unmedicated patients with schizophrenia and 60 normal controls and a group of 12 patients with schizotypal personality disorder. This confirmed smaller volumes of the medial dorsal and pulvinar in patients with schizophrenia and the pulvinar alone in patients with schizotypal personality disorder. Coregistered positon emission tomography scans with 18F-doxyglucose were available on the group of 101 and reduced metabolic rates in the medial dorsal and centromedian nuclei were confirmed. We obtained identical MRI on a total of 240 patients with schizophrenia ages 13-65, 78 patients with schizotypal disorder, and 223 normal controls (a total of 541 subjects) and have these images on line and ready for tracing. We carried out 2 functional MRI studies on the thalamus in normal controls with confirmation of functional activation in pulvinar and medial dorsal nucleus in attentional paradigms. In the next 4 years we propose 1) to develop methods for tracing the anterior nucleus of the thalamus, and trace the 4 nuclei in these subjects 2) to examine the relationship of age, sex, illness outcome and symptom patterns to thalamic nuclear volumes 3) contrast fMRI activation in normals and unmedicated and never medicated patients with schizophrenia using MRI templates for regional nuclear assessment and test interregional correlations in volume and activity 4) assess diffusion tensor anisotropy and angle of diffusion orientation in the internal capsule adjacent to the thalamus 5) examine correlations between nuclear volume and volume of regions of the brain that are reciprocally linked including the cingulate gyrus, the caudate and putamen, and the 44 Brodmann areas of the cortex. This project brings together the resources and imaging/anatomical researchers of the Mount Sinai Department of Psychiatry, the Neuroscience PET laboratory and the Department of Radiology.